Maryam Kaviani1, Somayeh Keshtkar2, Negar Azarpira3, Mahdokht Hossein Aghdaei1, Bita Geramizadeh1, Mohammad Hossein Karimi1, Alireza Shamsaeefar4, Nasrin Motazedian1, Saman Nikeghbalian4, Ismail H Al-Abdullah5, Mohammad Hossein Ghahremani6. 1. Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran. 2. Department of Molecular Medicine, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran; Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran. 3. Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran. Electronic address: Azarpiran@sums.ac.ir. 4. Shiraz Organ Transplant Center, Shiraz University of Medical Sciences, Shiraz, Iran. 5. Department of Translational Research and Cellular Therapeutics, Diabetes and Metabolism Research Institute, Beckman Research Institute of City of Hope, Duarte, USA. 6. Department of Molecular Medicine, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran; Department of Pharmacology-Toxicology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
Abstract
BACKGROUND AND PURPOSE: Islet transplantation is considered as a promising approach in the treatment of diabetes type 1. In this regard, optimal culture of the pancreatic islets is promising in the success of transplantation. In the present study, the effect of olesoxime, as an antiapoptotic substance, was evaluated on human islet culture. EXPERIMENTAL APPROACH: The pancreatic islets were isolated by mechanical and enzymatic techniques. After overnight recovery, the islets were treated by different concentrations of olesoxime for 24 and 72 h. Then, they were examined in terms of viability, apoptosis, genes and proteins expression including BAX, BCL2, active caspase-3, and insulin. Moreover, the islets function was evaluated through the glucose-induced insulin and C-peptide secretion assay. KEY RESULTS: Our findings showed that the islets increased in apoptosis and the decreased in viability after 72 h; also, insulin and C-peptide secretion reduced. However, in the presence of olesoxime, BAX/BCL2 ratio and the activation of caspase-3 were decreased. Therefore, olesoxime could improve the viability of the islets with the decrease of apoptosis. CONCLUSION: The application of olesoxime can reduce the stressful condition for the islets in vitro and subsequently improve their viability and functionality.
BACKGROUND AND PURPOSE: Islet transplantation is considered as a promising approach in the treatment of diabetes type 1. In this regard, optimal culture of the pancreatic islets is promising in the success of transplantation. In the present study, the effect of olesoxime, as an antiapoptotic substance, was evaluated on human islet culture. EXPERIMENTAL APPROACH: The pancreatic islets were isolated by mechanical and enzymatic techniques. After overnight recovery, the islets were treated by different concentrations of olesoxime for 24 and 72 h. Then, they were examined in terms of viability, apoptosis, genes and proteins expression including BAX, BCL2, active caspase-3, and insulin. Moreover, the islets function was evaluated through the glucose-induced insulin and C-peptide secretion assay. KEY RESULTS: Our findings showed that the islets increased in apoptosis and the decreased in viability after 72 h; also, insulin and C-peptide secretion reduced. However, in the presence of olesoxime, BAX/BCL2 ratio and the activation of caspase-3 were decreased. Therefore, olesoxime could improve the viability of the islets with the decrease of apoptosis. CONCLUSION: The application of olesoxime can reduce the stressful condition for the islets in vitro and subsequently improve their viability and functionality.
Authors: Mehdi Razavi; Rosita Primavera; Bhavesh D Kevadiya; Jing Wang; Mujib Ullah; Peter Buchwald; Avnesh S Thakor Journal: Nano Lett Date: 2020-09-21 Impact factor: 11.189